The long term goal of the application is to develop a treatment for antibiotic-resistant Staphylococcus aureus infections using human monoclonal antibodies. Methicillan-resistant S. aureus (MRSA) are a major cause of nosocomial infections worldwide, and effective treatment of these infections is currently managed with a relatively toxic antibiotic, vancomycin. Evidence supporting the protective role of humoral immune responses to S. aureus infections has been documented by several groups. The recent availability of transgenic mice that produce fully mature human immunoglobulins (HuMab mice), allows for the straightforward development of high-affinity specific human antibodies. This phase I proposal specifically aims to generate a panel of hybridomas that secrete high affinity human monoclonal antibodies specific for S. aureus surface antigens. These antibodies will be evaluated alone and in combination with clinically relevant strains of S. aureus using in vitro phagocytosis and killing assays. The ultimate goal of the project is to develop several antibodies to be used in combination for prevention of S. aureus infections in high-risk groups, or for treatment of individuals with MRSA infections. PROPOSED COMMERCIAL APPLICATION Human antibodies developed in this project may lead to a safe and effective treatment for the prevention and treatment of Staphylococcus aureus infections in humans.